Antihyperglycemic and Pancreatic Antioxidant Effects of Carica papaya Leaf Extract in Streptozotocin-Induced Diabetic Rats
DOI:
https://doi.org/10.56919/usci.2652.033Keywords:
carica papaya, oxidative stress, diabetes, pancreas, hyperglycemiaAbstract
Diabetes mellitus is a chronic metabolic disorder characterized by persistent hyperglycemia and progressive pancreatic β-cell damage, often exacerbated by oxidative stress. This study evaluates the antihyperglycemic, insulinotropic, antioxidant, and pancreatic cytoprotective effects of C. papaya leaf crude extract in streptozotocin (STZ)-induced diabetic rats. Thirty-six male Wistar rats were randomly and equally assigned into six groups: normal control, diabetic control, metformin-treated (100 mg/kg), crude Carica papaya extract-treated (200 mg/kg and 400 mg/kg), and n-hexane fraction-treated (200 mg/kg). Diabetes was induced using a single intraperitoneal injection of STZ (60 mg/kg). Over 21 days, fasting blood glucose, serum insulin levels, HOMA-IR and HOMA-β indices were assessed. Oxidative stress biomarkers, including superoxide dismutase (SOD), catalase (CAT), glutathione (GSH), and malondialdehyde (MDA), were measured in pancreatic tissues. Histological analysis of the pancreas was conducted to evaluate tissue integrity. One-Way ANOVA was used to compare means, and p<0.05 was considered statistically significant. The 200 mg/kg crude extract (CECP200) significantly reduced fasting blood glucose and improved insulin levels, HOMA-β, and HOMA-IR compared to the diabetic and metformin-treated groups (p < 0.05). CECP200 also restored antioxidant enzyme activities (SOD, CAT, GSH) and significantly reduced MDA levels, indicating protection against oxidative damage. Histopathological findings revealed partial preservation of islet architecture and reduced pancreatic necrosis in CECP200-treated rats, whereas the n-hexane fraction group showed less consistent histological recovery and mild inflammatory changes. C. papaya leaf crude extract shows strong antihyperglycemic, antioxidant, and pancreatic protective effects in diabetic rats, highlighting its potential as a complementary diabetes prevention and management, pending further investigation.
References
Agada, R., Thagriki, D., Lydia, D. E., Khusro, A., Alkahtani, J., Al Shaqha, M. M., Alwahibi, M. S., & Elshikh, M. S. (2021). Antioxidant and anti-diabetic activities of bioactive fractions of Carica papaya seeds extract. Journal of King Saud University - Science, 33 (2), 101342. DOI: https://doi.org/10.1016/j.jksus.2021.101342
Akanji, M. A., & Yakubu, M. T. (2000). α-Tocopherol protects against metabisulphite-induced tissue damage in rats. Nigerian Journal of Biochemistry and Molecular Biology, 15(2), 179-183.
Amin, A. H. (2021). Ameliorative effects of Carica papaya extracts against type II diabetes-induced myocardial pathology and dysfunction in albino rats. Environmental Science and Pollution Research, 28(41), 58232-58240. DOI: https://doi.org/10.1007/s11356-021-14843-0
Ansari, P., Reberio, A. D., Ansari, N. J., Kumar, S., Khan, J. T., Chowdhury, S., Abd El-Mordy, F. M., Hannan, J. M. A., Flatt, P. R., Abdel-Wahab, Y. H. A., & Seidel, V. (2025). Therapeutic potential of medicinal plants and their phytoconstituents in diabetes, cancer, infections, cardiovascular diseases, inflammation and gastrointestinal disorders. Biomedicines, 13(2). DOI: https://doi.org/10.3390/biomedicines13020454
Arunachalam, K., Sreeja, P. S., & Yang, X. (2022). The antioxidant properties of mushroom polysaccharides can potentially mitigate oxidative stress, beta-cell dysfunction and insulin resistance. Frontiers in Pharmacology, 13, 874474. DOI: https://doi.org/10.3389/fphar.2022.874474
Aschner, P., Karuranga, S., James, S., Simmons, D., Basit, A., Shaw, J. E., Wild, S. H., Ogurtsova, K., & Saeedi, P. (2021). The International Diabetes Federation's guide for diabetes epidemiological studies. Diabetes Research and Clinical Practice, 172. DOI: https://doi.org/10.1016/j.diabres.2020.108630
Babalola, B. A., Akinwande, A. I., Otunba, A. A., Adebami, G. E., Babalola, O., & Nwufo, C. (2024). Therapeutic benefits of Carica papaya: A review on its pharmacological activities and characterization of papain. Arabian Journal of Chemistry, 17(1), 105369. DOI: https://doi.org/10.1016/j.arabjc.2023.105369
Bhatti, J. S., Sehrawat, A., Mishra, J., Sidhu, I. S., Navik, U., Khullar, N., Kumar, S., Bhatti, G. K., & Reddy, P. H. (2022). Oxidative stress in the pathophysiology of type 2 diabetes and related complications: Current therapeutics strategies and future perspectives. Free Radical Biology and Medicine, 184, 114-134. DOI: https://doi.org/10.1016/j.freeradbiomed.2022.03.019
Bürgi, W., Briner, M., Franken, N., & Kessler, A.-C. (1988). One-step sandwich enzyme immunoassay for insulin using monoclonal antibodies. Clinical Biochemistry, 21(5), 311-314. DOI: https://doi.org/10.1016/S0009-9120(88)80087-0
Campos-Shimada, L. B., Hideo Gilglioni, E., Fernandes Garcia, R., Rizato Martins-Maciel, E., Luiza Ishii-Iwamoto, E., & Luzia Salgueiro-Pagadigorria, C. (2020). Superoxide dismutase: A review and a modified protocol for activities measurements in rat livers. Archives of Physiology and Biochemistry, 126(4), 292-299. DOI: https://doi.org/10.1080/13813455.2018.1520891
Clemente-Suárez, V. J., Martín-Rodríguez, A., Beltrán-Velasco, A. I., Rubio-Zarapuz, A., Martínez-Guardado, I., Valcárcel-Martín, R., & Tornero-Aguilera, J. F. (2025). Functional and therapeutic roles of plant-derived antioxidants in type 2 diabetes mellitus: Mechanisms, challenges, and considerations for special populations. Antioxidants, 14(6). DOI: https://doi.org/10.3390/antiox14060725
Dinić, S., Arambašić Jovanović, J., Uskoković, A., Mihailović, M., Grdović, N., Tolić, A., Rajić, J., Đorđević, M., & Vidaković, M. (2022). Oxidative stress-mediated beta cell death and dysfunction as a target for diabetes management. Frontiers in Endocrinology, 13, 1006376. DOI: https://doi.org/10.3389/fendo.2022.1006376
Ebifa, J. O., Elechi-Amadi, H., Abiakam, H., & Briggs, O. N. (2021). Comparative effects of Carica papaya, avocado pear and ginger extracts on the histological structure of the pancreas of streptozotocin-induced diabetic rats. Asian Journal of Medical Principles and Clinical Practice, 4(4), 1-11.
Eguchi, N., Vaziri, N. D., Dafoe, D. C., & Ichii, H. (2021). The role of oxidative stress in pancreatic β cell dysfunction in diabetes. International Journal of Molecular Sciences, 22(4). DOI: https://doi.org/10.3390/ijms22041509
Ekeuku, S. O., Chong, P. N., Chan, H. K., Mohamed, N., Froemming, G. R. A., & Okechukwu, P. N. (2022). Spirulina supplementation improves bone structural strength and stiffness in streptozocin-induced diabetic rats. Journal of Traditional and Complementary Medicine, 12(3), 225-234. DOI: https://doi.org/10.1016/j.jtcme.2021.07.010
Flood, D., Seiglie, J. A., Dunn, M., Tschida, S., Theilmann, M., Marcus, M. E., Brian, G., Norov, B., Mayige, M. T., & Gurung, M. S. (2021). The state of diabetes treatment coverage in 55 low-income and middle-income countries: A cross-sectional study of nationally representative, individual-level data in 680,102 adults. The Lancet Healthy Longevity, 2(6), e340-e351. DOI: https://doi.org/10.1016/S2666-7568(21)00089-1
Ghorat, F., Mosavat, S. H., Hadigheh, S., Kouhpayeh, S. A., Naghizadeh, M. M., Rashidi, A. A., & Hashempur, M. H. (2024). Prevalence of complementary and alternative medicine use and its associated factors among Iranian diabetic patients: A cross-sectional study. Current Therapeutic Research, 100, 100746. DOI: https://doi.org/10.1016/j.curtheres.2024.100746
Giglio, R. V., Papanas, N., Rizvi, A. A., Ciaccio, M., Patti, A. M., Ilias, I., Pantea Stoian, A., Sahebkar, A., Janez, A., & Rizzo, M. (2022). An update on the current and emerging use of thiazolidinediones for type 2 diabetes. Medicina, 58(10), 1475. DOI: https://doi.org/10.3390/medicina58101475
Hariono, M., Julianus, J., Djunarko, I., Hidayat, I., Adelya, L., Indayani, F., Auw, Z., Namba, G., & Hariyono, P. (2021). The future of Carica papaya leaf extract as an herbal medicine product. Molecules, 26(22), 6922. DOI: https://doi.org/10.3390/molecules26226922
International Diabetes Federation. (2021). IDF Diabetes Atlas (10th ed.). IDF.
Islam, K., Islam, R., Nguyen, I., Malik, H., Pirzadah, H., Shrestha, B., Lentz, I. B., Shekoohi, S., & Kaye, A. D. (2025). Diabetes mellitus and associated vascular disease: Pathogenesis, complications, and evolving treatments. Advances in Therapy, 1-20. DOI: https://doi.org/10.1007/s12325-025-03185-9
Kumari Sinha, R., Pratap, R., & Chandra Varm, M. (2018). Hypoglycemic activity of Carica papaya leaf aqueous extract in normal and diabetic mice. International Journal of Advances in Scientific Research and Engineering, 4(6), 12-16. DOI: https://doi.org/10.31695/IJASRE.2018.32747
Lekshmi, R. K., Rajesh, R., & Mini, S. (2015). Ethyl acetate fraction of Cissus quadrangularis stem ameliorates hyperglycaemia-mediated oxidative stress and suppresses inflammatory response in nicotinamide/streptozotocin induced type 2 diabetic rats. Phytomedicine, 22(10), 952-960. DOI: https://doi.org/10.1016/j.phymed.2015.06.014
Mathu, R., Abarnadevika, A., & Ariharasivakumar, G. (2021). A study of biguanides in the care of type II diabetes mellitus. J Pharm Sci Drug Discov, 1(1), 1-9.
Morolahun, E. A., Ajao, F. O., & Pemba, S. K. (2019). Antidiabetic effect of aqueous extract of ripe Carica papaya Linnaeus seed in alloxan-induced diabetic albino rats. Journal of Diabetes and Endocrinology, 10(2), 13-17. DOI: https://doi.org/10.5897/JDE2018.0127
Nwogueze, B. C., Ojieh, A. E., Aloamaka, C. P., Igweh, J. C., & Onyesom, I. (2021). Levels of glutathione-related antioxidants in some tissues of stressed Wistar rats. Indian Journal of Physiology and Pharmacology, 65(3), 167-176. DOI: https://doi.org/10.25259/IJPP_41_2020
Nxumalo, M. B., Ntanzi, N., Kumalo, H. M., & Khan, R. B. (2024). Mitigating hyperglycaemic oxidative stress in HepG2 cells: The role of Carica papaya leaf and root extracts in promoting glucose uptake and antioxidant defence. Nutrients, 16(20), 3496. DOI: https://doi.org/10.3390/nu16203496
Nyakundi, B. B., & Yang, J. (2023). Uses of papaya leaf and seaweed supplementations for controlling glucose homeostasis in diabetes. International Journal of Molecular Sciences, 24(7), 6846. DOI: https://doi.org/10.3390/ijms24076846
Nyakundi, B. B., Wall, M. M., & Yang, J. (2024). Supplementation of papaya leaf juice has beneficial effects on glucose homeostasis in high fat/high sugar-induced obese and prediabetic adult mice. BMC Complementary Medicine and Therapies, 24(1), 18. DOI: https://doi.org/10.1186/s12906-023-04320-1
Ogunlakin, A. D., Onifade, T. R., Ojo, O. A., Adesanya, E. O., Berena, G. A., Ayeni, P. O., Omolekan, T. O., Ogunlakin, M. A., Iyinkristi, D. A., & Sonibare, M. A. (2023). Antidiabetic potential of Carica papaya L. and its constituents: From folkloric uses to products development. Bioactive Compounds in Health and Disease, 6(6), 126-144. DOI: https://doi.org/10.31989/bchd.v6i6.1108
Ogurtsova, K., Guariguata, L., Barengo, N. C., Ruiz, P. L.-D., Sacre, J. W., Karuranga, S., Sun, H., Boyko, E. J., & Magliano, D. J. (2022). IDF Diabetes Atlas: Global estimates of undiagnosed diabetes in adults for 2021. Diabetes Research and Clinical Practice, 183, 109118. DOI: https://doi.org/10.1016/j.diabres.2021.109118
Olszowy-Tomczyk, M., Paprotny, Ł., Celejewska, A., Szewczak, D., & Wianowska, D. (2022). Comparison of the antioxidant properties of serum and plasma samples as well as glutathione under environmental and pharmacological stress factors involving different classes of drugs. Environmental Toxicology and Pharmacology, 94, 103936. DOI: https://doi.org/10.1016/j.etap.2022.103936
Omiyale, O. C., Ogunniran, B. I., Ezeh, M. O., Yussuf, M. D., Oparah, C. D., & Isshak, F. (2024). Hypoglycemic and antioxidants activities of Carica papaya leaves. International Journal of Advanced Biological and Biomedical Research, 12, 141-154.
Papachristoforou, E., Lambadiari, V., Maratou, E., & Makrilakis, K. (2020). Association of glycemic indices (hyperglycemia, glucose variability, and hypoglycemia) with oxidative stress and diabetic complications. Journal of Diabetes Research, 2020, 7489795. DOI: https://doi.org/10.1155/2020/7489795
Roy, J. R., Janaki, C. S., Jayaraman, S., Veeraraghavan, V. P., Periyasamy, V., Balaji, T., Vijayamalathi, M., Bhuvaneswari, P., & Swetha, P. (2023). Hypoglycemic potential of Carica papaya in liver is mediated through IRS-2/PI3K/SREBP-1c/GLUT2 signaling in high-fat-diet-induced type-2 diabetic male rats. Toxics, 11(3). DOI: https://doi.org/10.3390/toxics11030240
Sagita, M. B., Turchan, A., Utomo, B., Al Fauzi, A., & Fauziah, D. (2022). Expression malondialdehyde (MDA) of brain after injury with the extract of kencur (Kaempferia galanga L.): Experimental study Wistar rats. International Journal of Health and Medical Sciences, 5(1), 114-121. DOI: https://doi.org/10.21744/ijhms.v5n1.1848
Sharma, A., Sharma, R., Sharma, M., Kumar, M., Barbhai, M. D., Lorenzo, J. M., Sharma, S., Samota, M. K., Atanassova, M., Caruso, G., Naushad, M., Radha, Chandran, D., Prakash, P., Hasan, M., Rais, N., Dey, A., Mahato, D. K., Dhumal, S., ... Mekhemar, M. (2022). Carica papaya L. leaves: Deciphering its antioxidant bioactives, biological activities, innovative products, and safety aspects. Oxidative Medicine and Cellular Longevity, 2022, 2451733. DOI: https://doi.org/10.1155/2022/2451733
Siregar, U. A., Sadhana, U., & Prajoko, Y. W. (2020). Smoke exposure effect of motor vehicles against blood sugar levels and pancreatic histopathology Wistar rats. International Journal of Scientific and Technology Research, 9(3), 1828-1831.
Sitompul, F., Christy, C. A. D., Sani, Y., & Simatupang, A. (2024). Histopathological picture of the pancreas of mice (Mus musculus) diabetes induced by streptozotocin-sukrosa by giving papaya seed extract (Carica papaya L.). Journal of Social Research, 3(3), 1-11. DOI: https://doi.org/10.55324/josr.v3i3.1962
Soib, H. H., Ismail, H. F., Husin, F., Abu Bakar, M. H., Yaakob, H., & Sarmidi, M. R. (2020). Bioassay-guided different extraction techniques of Carica papaya (Linn.) leaves on in vitro wound-healing activities. Molecules, 25(3). DOI: https://doi.org/10.3390/molecules25030517
Solikhah, T. I., Setiawan, B., & Ismukada, D. R. (2020). Antidiabetic activity of papaya leaf extract (Carica papaya L.) isolated with maceration method in alloxan-induced diabetic mice. Systematic Reviews in Pharmacy, 11(9), 774-778.
Tan, Y. C., Abdul Sattar, M., Ahmeda, A. F., Abdul Karim Khan, N., Murugaiyah, V., Ahmad, A., Hassan, Z., Kaur, G., Abdulla, M. H., & Johns, E. J. (2020). Apocynin and catalase prevent hypertension and kidney injury in Cyclosporine A-induced nephrotoxicity in rats. PLoS ONE, 15(4), e0231472. DOI: https://doi.org/10.1371/journal.pone.0231472
Tomlinson, B., Patil, N. G., Fok, M., Chan, P., & Lam, C. W. K. (2022). The role of sulfonylureas in the treatment of type 2 diabetes. Expert Opinion on Pharmacotherapy, 23(3), 387-403. DOI: https://doi.org/10.1080/14656566.2021.1999413
Tran, N., Pham, B., & Le, L. (2020). Bioactive compounds in anti-diabetic plants: From herbal medicine to modern drug discovery. Biology, 9(9). DOI: https://doi.org/10.3390/biology9090252
Unuofin, J. O., & Lebelo, S. L. (2020). Antioxidant effects and mechanisms of medicinal plants and their bioactive compounds for the prevention and treatment of type 2 diabetes: An updated review. Oxidative Medicine and Cellular Longevity, 2020, 1356893. DOI: https://doi.org/10.1155/2020/1356893
Verma, A. K., Goyal, Y., Bhatt, D., Dev, K., Alsahli, M. A., Rahmani, A. H., & Almatroudi, A. (2021). A compendium of perspectives on diabetes: A challenge for sustainable health in the modern era. Diabetes, Metabolic Syndrome and Obesity, 2775-2787. DOI: https://doi.org/10.2147/DMSO.S304751
Yoon, H., Jeon, D. J., Park, C. E., You, H. S., & Moon, A. E. (2016). Relationship between homeostasis model assessment of insulin resistance and beta cell function and serum 25-hydroxyvitamin D in non-diabetic Korean adults. Journal of Clinical Biochemistry and Nutrition, 59(2), 139-144. DOI: https://doi.org/10.3164/jcbn.15-143
Zhu, B. T. (2022). Pathogenic mechanism of autoimmune diabetes mellitus in humans: Potential role of streptozotocin-induced selective autoimmunity against human islet β-cells. Cells, 11(3), 492. DOI: https://doi.org/10.3390/cells11030492
Downloads
Published
Issue
Section
License
Copyright (c) 2026 Oluwafemi Francis Adebayo, Gideon Egesie, Odu Samuel Odeh (Author)
This work is licensed under a Creative Commons Attribution-NonCommercial 4.0 International License.
UMYU Scientifica recognizes the importance of protecting authors’ intellectual property while promoting the free exchange of scientific knowledge. The journal adopts a copyright-retention model that empowers authors to maintain ownership of their work while granting the journal rights necessary for publication and dissemination.
1. Copyright Ownership
Authors publishing with UMYU Scientifica retain full copyright and publishing rights to their work. By submitting a manuscript, authors agree to grant the journal a non-exclusive license to publish, reproduce, distribute, and archive the article in all forms and media for the purpose of scholarly communication.
2. Licensing Terms
All articles are published under the Creative Commons Attribution–NonCommercial (CC BY-NC) license.
This license permits others to:
- Share - copy and redistribute the material in any medium or format.
- Adapt - remix, transform, and build upon the material.
- For non-commercial purposes only, provided that proper credit is given to the original author(s) and UMYU Scientifica as the source, a link to the license is provided, and any modifications are clearly indicated.
Commercial reuse or distribution of the content requires written permission from both the author and the editorial office.
3. Author Rights
Authors are free to:
- Deposit all versions of their manuscript (preprint, accepted version, and published version) in institutional, disciplinary, or public repositories without embargo.
- Use and distribute their published article for non-commercial scholarly purposes, including teaching, conference presentations, and research sharing.
- Include their work in future books, theses, or compilations, provided proper citation to the journal is made.
4. Publisher’s Rights
Upon publication, UMYU Scientifica retains the right to:
- Host, index, and disseminate the article through the journal’s website and partner databases.
- Archive the content in long-term preservation systems such as the PKP Preservation Network (PKP-PN) and the Umaru Musa Yar’adua University Institutional Repository.
5. Attribution and Citation
Users must give appropriate credit to the author(s), include a link to the article’s DOI or the journal webpage, and indicate if changes were made. Proper citation is required whenever the work is reused or referenced.
6. License Reference
For detailed terms of use, please refer to the Creative Commons Attribution–NonCommercial 4.0 International License (CC BY-NC 4.0):
https://creativecommons.org/licenses/by-nc/4.0/
